Patients with hypertrophic cardiomyopathy(HCM) frequently experience chest pain that occurs with variable threshold of onset and is often prolonged in duration. This study was designed to evaluate the effect of a pharmacologic vasoconstrictor agent, ergonovine, on the coronary vasculature of patients with HCM. Fifteen patients with HCM and chest pain despite angiographically normal appearing coronary arteries underwent a pacing study with measurement of coronary flow, and myocardial mechanics and metabolism. Afterward, a repeat pacing study was performed after administration of ergonovine. HCM patients were found to have high resting coronary flow as expected due to the increased muscle mass associated with this disease. Eight HCM patients demonstrated a fall in coronary flow at high paced heart rates after an initial rise in flow at lower paced heart rates. This fall in flow was associated with a striking elevation in left ventricular filling pressure and metabolic evidence of ischemia. These same patients demonstrated vasoconstriction of the small coronary arteries or arteriold during pacing after ergonovine. This sensitivity to a vasoconstrictor stimulus (possibly because coronary arterioles are maximally dilated) may explain the variation in anginal threshold many HCM patients experience.